The effect of storage temperature fluctuations on the stability of biochemical analytes in blood serum
-
Helmuth Haslacher
,
Thomas Szekeres
Abstract
Background:
Irreproducibility of scientific results constitutes an undesirably onerous economic burden and is in many cases caused by low-quality materials. Therefore, researchers are increasingly devoting their attention to the bioresources they use. In turn, those bioresources are required to validate their preanalytical processes in order to ensure best possible quality. The present study thus aimed to evaluate the impact of repeated temperature fluctuations, as they occur in most research biobanks due to repetitive opening and closing of freezer doors, on the stability of 26 biochemical analytes.
Methods:
Serum of 43 individuals was randomly assigned to a fluctuation (n=21) and a control group (n=22). Serum of the fluctuation group underwent controlled temperature fluctuations (30 fluctuations <−75°C – <−65°C – <−75°C under real-life freezer conditions within 21 days). Control sera were stored at constant conditions. After 10, 20, and 30 fluctuations, results derived from the fluctuation group were compared to baseline and to the control group by means of general linear models.
Results:
Sixteen biomarkers showed statistically significant changes over time, whereas only seven of those presented with diagnostically/clinically relevant changes at certain time points (aspartate aminotransferase, amylase, calcium, uric acid, creatinine, inorganic phosphate and total protein). However, there was no difference between the fluctuation and the control group.
Conclusions:
Some serum analytes are influenced by storage, even at temperatures as low as <−70°C. In contrast, we found no evidence that complex temperature fluctuations produced by storage of and access to biospecimens in biobank freezers generate any additional variability.
Acknowledgments
This study was conducted in the framework of the MedUni Wien Biobank project (http://www.biobank.at).
Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
Research funding: None declared.
Employment or leadership: None declared.
Honorarium: None declared.
Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.
References
1. Freedman LP, Cockburn IM, Simcoe TS. The Economics of Reproducibility in Preclinical Research. PLoS Biol 2015;13:e1002165.10.1371/journal.pbio.1002165Search in Google Scholar
2. Ellervik C, Vaught J. Preanalytical variables affecting the integrity of human biospecimens in biobanking. Clin Chem 2015;61:914–34.10.1373/clinchem.2014.228783Search in Google Scholar
3. Lippi G, Guidi GC, Mattiuzzi C, Plebani M. Preanalytical variability: the dark side of the moon in laboratory testing. Clin Chem Lab Med 2006;44:358–65.10.1515/CCLM.2006.073Search in Google Scholar
4. Craig WY, Ledue TB. The effects of long term storage on serum Lp(a) levels. Atherosclerosis 1992;93:261.10.1016/0021-9150(92)90264-HSearch in Google Scholar
5. Wigmore JG. Blood ethanol concentrations are less stable than serum or plasma upon storage because of oxyhemoglobin-mediated oxidation of ethanol to acetaldehyde. J Anal Toxicol 2009;33:182–3.10.1093/jat/33.3.182Search in Google Scholar PubMed
6. Gaye A, Peakman T, Tobin MD, Burton PR. Understanding the impact of pre-analytic variation in haematological and clinical chemistry analytes on the power of association studies. Int J Epidemiol 2014;43:1633–44.10.1093/ije/dyu127Search in Google Scholar PubMed PubMed Central
7. Ikeda K, Ichihara K, Hashiguchi T, Hidaka Y, Kang D, Maekawa M, et al. Evaluation of the short-term stability of specimens for clinical laboratory testing. Biopreserv Biobank 2015;13:135–43.10.1089/bio.2014.0072Search in Google Scholar PubMed
8. Ollier W, Sprosen T, Peakman T. UK Biobank: from concept to reality. Pharmacogenomics 2005;6:639–46.10.2217/14622416.6.6.639Search in Google Scholar PubMed
9. Zander J, Bruegel M, Kleinhempel A, Becker S, Petros S, Kortz L, et al. Effect of biobanking conditions on short-term stability of biomarkers in human serum and plasma. Clin Chem Lab Med 2014;52:629–39.10.1515/cclm-2013-0705Search in Google Scholar PubMed
10. Polestar Cooling Ltd. UF 756 Ultra Cold Freezer [updated 2014-04-29]. Available from: http://www.polestarcooling.com/dometic.php?model=UF756.Search in Google Scholar
11. Benjamini Y, Hochberg Y. Controlling the false discovery rate: a practical and powerful approach to multiple testing. J Royal Stat Soc Series B (Methodological) 1995;57:289–300.10.1111/j.2517-6161.1995.tb02031.xSearch in Google Scholar
12. Zander J, Bruegel M, Kleinhempel A, Becker S, Petros S, Kortz L, et al. Effect of biobanking conditions on short-term stability of biomarkers in human serum and plasma. Clin Chem Lab Med 2014;52:629–39.10.1515/cclm-2013-0705Search in Google Scholar PubMed
13. Fraser CG. Reference change values. Clin Chem Lab Med 2012;50:807–12.10.1515/cclm.2011.733Search in Google Scholar PubMed
14. Huang GT. An integrated, module-based biomarker discovery framework. Doctoral dissertation, University of Pittsburgh, 2014.Search in Google Scholar
15. Taylor EC, Sethi B. Stability of 27 biochemistry analytes in storage at a range of temperatures after centrifugation. Br J Biomed Sci 2011;68:147–57.10.1080/09674845.2011.11730343Search in Google Scholar PubMed
16. Wilson SS, Guillan RA, Hocker EV. Studies of the stability of 18 chemical constituents of human serum. Clin Chem 1972;18:1498–503.10.1093/clinchem/18.12.1498Search in Google Scholar
17. Cuhadar S, Koseoglu M, Atay A, Dirican A. The effect of storage time and freeze-thaw cycles on the stability of serum samples. Biochemia Medica 2013;23:70–7.10.11613/BM.2013.009Search in Google Scholar PubMed PubMed Central
18. Alberghina D, Casella S, Giannetto C, Marafioti S, Piccione G. Effect of storage time and temperature on the total protein concentration and electrophoretic fractions in equine serum. Can J Vet Res 2013;77:293–6.Search in Google Scholar
19. Jansen EH, Beekhof PK, Cremers JW, Viezeliene D, Muzakova V, Skalicky J. Long-term stability of parameters of antioxidant status in human serum. Free Radic Res 2013;47:535–40.10.3109/10715762.2013.797969Search in Google Scholar PubMed
20. Askenazi DJ, Moore JF, Fineberg N, Koralkar R, Clevenger S, Sharer JD. Comparison of methods, storage conditions, and time to analysis of serum and urine creatinine measured from microsamples by liquid chromatography mass spectrometery (lc/ms) vs. Jaffe. J Clin Lab Anal 2014;28:405–8.10.1002/jcla.21701Search in Google Scholar PubMed PubMed Central
21. Comstock GW, Burke AE, Norkus EP, Gordon GB, Hoffman SC, Helzlsouer KJ. Effects of repeated freeze-thaw cycles on concentrations of cholesterol, micronutrients, and hormones in human plasma and serum. Clin Chem 2001;47:139–42.10.1093/clinchem/47.1.139Search in Google Scholar
©2017 Walter de Gruyter GmbH, Berlin/Boston
Articles in the same Issue
- Frontmatter
- Editorials
- Opportunities and drawbacks of nonstandard body fluid analysis
- How I first met Dr. Morton K. Schwartz
- Reviews
- Measurement of thyroglobulin, calcitonin, and PTH in FNA washout fluids
- Quality control materials for pharmacogenomic testing in the clinic
- Modulating thrombotic diathesis in hereditary thrombophilia and antiphospholipid antibody syndrome: a role for circulating microparticles?
- Opinion Papers
- Advances in laboratory diagnosis of hereditary spherocytosis
- Analytical performance specifications for external quality assessment – definitions and descriptions
- Genetics and Molecular Diagnostics
- Differences between quantification of genotype 3 hepatitis C virus RNA by Versions 1.0 and 2.0 of the COBAS AmpliPrep/COBAS TaqMan HCV Test
- General Clinical Chemistry and Laboratory Medicine
- Estimating the intra- and inter-individual imprecision of manual pipetting
- Effect of multiple freeze-thaw cycles on selected biochemical serum components
- The effect of storage temperature fluctuations on the stability of biochemical analytes in blood serum
- Comparison of ex vivo stability of copeptin and vasopressin
- Physiologic changes of urinary proteome by caffeine and excessive water intake
- Assessment of autoantibodies to interferon-ω in patients with autoimmune polyendocrine syndrome type 1: using a new immunoprecipitation assay
- Reference Values and Biological Variations
- Within-day biological variation and hour-to-hour reference change values for hematological parameters
- Relationship between anti-Müllerian hormone and antral follicle count across the menstrual cycle using the Beckman Coulter Access assay in comparison with Gen II manual assay
- Cardiovascular Diseases
- Low-grade inflammation and tryptophan-kynurenine pathway activation are associated with adverse cardiac remodeling in primary hyperparathyroidism: the EPATH trial
- Infectious Diseases
- Comparison between procalcitonin and C-reactive protein in predicting bacteremias and confounding factors: a case-control study
- Monitoring of procalcitonin but not interleukin-6 is useful for the early prediction of anastomotic leakage after colorectal surgery
- Activation of the tryptophan/serotonin pathway is associated with severity and predicts outcomes in pneumonia: results of a long-term cohort study
- Letters to the Editor
- Incidental findings of monoclonal proteins from carbohydrate-deficient transferrin analysis using capillary electrophoresis
- IgD-λ myeloma with extensive free light-chain excretion: a diagnostic pitfall in the identification of monoclonal gammopathies
- 25-Hydroxyvitamin D threshold values should be age-specific
- Effect of dabigatran treatment at therapeutic levels on point-of-care international normalized ratio (INR)
- Alkaline phosphatase activity – pH impact on the measurement result
- Cyst hydatid and cancer: the myth continues
- Role of activated platelets in severe acne scarring and adaptive immunity activation
- Towards a random-access LC-MS/MS model for busulfan analysis
Articles in the same Issue
- Frontmatter
- Editorials
- Opportunities and drawbacks of nonstandard body fluid analysis
- How I first met Dr. Morton K. Schwartz
- Reviews
- Measurement of thyroglobulin, calcitonin, and PTH in FNA washout fluids
- Quality control materials for pharmacogenomic testing in the clinic
- Modulating thrombotic diathesis in hereditary thrombophilia and antiphospholipid antibody syndrome: a role for circulating microparticles?
- Opinion Papers
- Advances in laboratory diagnosis of hereditary spherocytosis
- Analytical performance specifications for external quality assessment – definitions and descriptions
- Genetics and Molecular Diagnostics
- Differences between quantification of genotype 3 hepatitis C virus RNA by Versions 1.0 and 2.0 of the COBAS AmpliPrep/COBAS TaqMan HCV Test
- General Clinical Chemistry and Laboratory Medicine
- Estimating the intra- and inter-individual imprecision of manual pipetting
- Effect of multiple freeze-thaw cycles on selected biochemical serum components
- The effect of storage temperature fluctuations on the stability of biochemical analytes in blood serum
- Comparison of ex vivo stability of copeptin and vasopressin
- Physiologic changes of urinary proteome by caffeine and excessive water intake
- Assessment of autoantibodies to interferon-ω in patients with autoimmune polyendocrine syndrome type 1: using a new immunoprecipitation assay
- Reference Values and Biological Variations
- Within-day biological variation and hour-to-hour reference change values for hematological parameters
- Relationship between anti-Müllerian hormone and antral follicle count across the menstrual cycle using the Beckman Coulter Access assay in comparison with Gen II manual assay
- Cardiovascular Diseases
- Low-grade inflammation and tryptophan-kynurenine pathway activation are associated with adverse cardiac remodeling in primary hyperparathyroidism: the EPATH trial
- Infectious Diseases
- Comparison between procalcitonin and C-reactive protein in predicting bacteremias and confounding factors: a case-control study
- Monitoring of procalcitonin but not interleukin-6 is useful for the early prediction of anastomotic leakage after colorectal surgery
- Activation of the tryptophan/serotonin pathway is associated with severity and predicts outcomes in pneumonia: results of a long-term cohort study
- Letters to the Editor
- Incidental findings of monoclonal proteins from carbohydrate-deficient transferrin analysis using capillary electrophoresis
- IgD-λ myeloma with extensive free light-chain excretion: a diagnostic pitfall in the identification of monoclonal gammopathies
- 25-Hydroxyvitamin D threshold values should be age-specific
- Effect of dabigatran treatment at therapeutic levels on point-of-care international normalized ratio (INR)
- Alkaline phosphatase activity – pH impact on the measurement result
- Cyst hydatid and cancer: the myth continues
- Role of activated platelets in severe acne scarring and adaptive immunity activation
- Towards a random-access LC-MS/MS model for busulfan analysis
